Tissue engineering has shown promise for the development of constructs to facilitate large volume soft tissue augmentation in reconstructive and cosmetic plastic surgery (Flynn et al., Organogenesis, 4(4), 228-351 (2008)). The treatment of post-operative, congenital or post-traumatic loss of the subcutaneous fat layer can result in scar tissue deformity, and a loss of function (Katz et al., Clin Plast Surg, 26(4, 587-603, viii (1999)). Current Clinical Strategies for soft tissue augmentation primarily involve autologous, allogeneic and alloplastic materials. Free fat transfer yields unsatisfactory and unpredictable results, with varying degrees of graft resorption due to a lack of supporting vasculature (Peer, Am J Surg, 92(1), 40-7 (1956)). Thus, only small defects can be corrected with injected autologous fat, and even these limited applications require repeated treatments to maintain the desired volume (Huss et al., Scand J Plast Reconstr Surg Hand Surg, 36(3): p. 166-71 (2002)).
For the majority of women who undergo reconstruction after a mastectomy, typically the final step in the reconstruction process involves nipple areola complex (NAC) reconstruction. Results of currently available NAC reconstruction techniques are unpredictable; they may lose shape and fade in a few years. Studies highlight that patients with loss of the nipple and areola from cancer continue to experience psychological distress even long after breast mound reconstruction has taken place.
Indications where use of a VFU may be appropriate include without limitation nipple areola reconstruction after the initial nipple areola complex (NAC) is removed during mastectomy; filling the void created from tumor resection such as the indentation formed under the skin after a tumorous tissue is removed, for example but not limited to, melanoma or soft tissue sarcoma, or after a lumpectomy; for constructing features missing or deformed due to congenital defects, for example but not limited to Poland's syndrome and Parry-Romberg syndrome; for filling voids created from injury, disease or trauma such as auto accidents or certain wounds; and cosmetic applications such as lip, breast, or calf augmentation, buttock implant, cheek and other facial implants.
Thus, there is a need for tissue engineered devices suitable for dimensionally filling a void or defect in a mammal, such as the result of surgical resection, wounds or other traumatic injuries, a birth defect, or certain other malformations.
A fundamental challenge in the field of Tissue Engineering is the formation and culture of thick tissue engineered constructs. Thick constructs, on the order of several millimeters to centimeters, are often needed to replace or repair clinically relevant defects. In culture, however, nutrient perfusion is typically limited to a few hundred um in constructs with high cellular density. Highly metabolic cell structures will begin to starve unless nutrient exchange can be facilitated (Patel and Mikos, J Biomater Sci Polym Ed., 15(6):701-26 (2004)). In living organisms the nutrient exchange is handled by the host's vasculature, using blood to supply oxygen and nutrients, and to remove CO2 and waste products. In the lab, an easy alternative to complex vasculature is desired to allow thick tissues to be produced.
Thus, there is also a need for tissue engineered devices with appreciable thickness for repairing of clinically relevant defects and certain cosmetic applications.